New Antibiotics and New Resistance

In many ways, the fight against antibiotic resistance is already lost; preventing bacterial disease requires thoughtful new approaches

Carlos Amábile-Cuevas

Antibiotics were treated as miracle drugs when they first became available half a century ago. But their popularity rapidly led to overuse. Over the last decade, it has become well-known that antibiotics are losing their effectiveness as bacteria evolve resistance against them and new drugs only rarely reach the market. Bacteria can acquire drug resistance in a multitude of ways, so getting around the resistance problem is not a straightforward matter. Pharmaceutical companies have just recently revived efforts to develop new antibiotics. But preventing a future in which bacteria are once again widespread killers requires more than one approach-among them, the rational use of antibiotics in health care and agriculture, improved techniques for developing new drugs and new perspectives on how to live with the infectious creatures that share the planet with us.

Bacterial infections have been a scourge on humankind for millennia. Plague, tuberculosis, wound infections and typhoid fever have caused historical as well as personal tragedies. No wonder, then, that antibiotics were greeted as miracle drugs. For a few decades the success of antibiotic therapies was remarkable, but enthusiasm for them led to abuses. Observers disregarded the early emergence of resistant bacteria; a number of new antibiotics were still being discovered, suggesting that effective drugs would always be available. With infections deemed under control, pharmaceutical companies lost interest in developing new antibiotics.

After decades of complacency and just 50 years after the first clinical use of an antibiotic, penicillin, the public health threat posed by antibiotic resistance finally gained widespread attention. Resistance made the cover of Time and Newsweek in the early 1990s; now, most people know that antibiotics can fail. Over nearly 20 years, from the early 1980s to the late 1990s, not a single truly new antibiotic was introduced into clinical use. Even now, barely a trickle has reached the market since 1999. Meanwhile, resistance keeps evolving, and drugs are rapidly losing their efficacy, resulting in increased treatment costs, loss of labor time and, of course worst of all, lost lives. My colleagues and I reviewed how bacteria evolve so quickly towards resistance some years ago ("Antibiotic Resistance," July-August 1995). Here I will discuss new discoveries on the biology of resistance, as well as efforts to either restrain or circumvent resistant organisms. In the struggle against antibiotic resistance, science is providing useful tools, and physicians are slowly realizing that antibiotics are simultaneously powerful and dangerous drugs. Ultimately, though, we will all need to change the way we deal with bacteria in the coming "post-antibiotic era." ...